Defining the contributions of proprioception to goal-directed reaching movements

定义本体感觉对目标导向的到达运动的贡献

• 批准号: 10425139
• 负责人: Akira Nagamori
• 金额: $ 7.01万
• 依托单位: SALK INSTITUTE FOR BIOLOGICAL STUDIES
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-07-01 至 2024-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10425139
• 关键词: Acceleration; Address; Affect; Afferent Pathways; Agonist; Animals; Automobile Driving; Behavior; Behavioral Paradigm; Biophysics; Cerebellar Diseases; Characteristics; Clinical; Clinical Research; Computer Models; Data; Deafferentation procedure; Deceleration; Diagnosis; Disease; Elbow; Ensure; Environment; Extensor; Feedback; Flexor; Forelimb; Foundations; Future; Genetic; Goals; Impairment; Injury; Interneurons; Joystick; Knowledge; Lead; Limb structure; Logic; Mediating; Methods; Modeling; Molecular Genetics; Motor; Movement; Movement Disorders; Mus; Muscle; Nervous system structure; Neurons; Pathway interactions; Pattern; Performance; Phase; Proprioception; Quality of life; Role; Sensory; Signal Transduction; Speed; Spinal; Stereotyping; Stroke; Structure; System; Testing; Viral; Work; antagonist; behavior observation; defined contribution; experimental study; genetic manipulation; improved; insight; kinematics; limb movement; motor deficit; motor impairment; mouse model; nervous system disorder; neural circuit; neuromechanism; optogenetics; presynaptic; recruit; sensorimotor system; theories; tool

Project Summary The ability to perform rapid, goal-directed movements accurately and efficiently is critical for interacting with the environment. These movements have provided a key behavioral paradigm for experimental and clinical study, helping to establish theories of sensorimotor control and to characterize motor impairments in many neurological disorders. The accurate execution of rapid, goal-directed movements is enabled by the characteristic, reciprocal activation of opposing muscles that accelerate and decelerate the limb in a temporally precise manner. Many sensorimotor disorders across the nervous system (e.g. sensory deafferentation and cerebellar disease) disrupt this characteristic muscle activation, leading to impaired motor performance. Therefore, the emergence and disruption of this stereotyped pattern of muscle recruitment offer theoretical and clinical insights into how sensorimotor circuits enable speed and accuracy. Yet the neural mechanisms that establish and control this reciprocal muscle recruitment remain elusive, in large part because the relative contribution of proprioceptive feedback from the muscles has not been clearly established. Although behavioral observations and computational models have implicated proprioceptive feedback in coordinating limb movements, the direct causal role of these sensory pathways in driving temporally precise muscle activation in intact, behaving animals has been difficult to investigate. The challenge is due, in part, to the inability of traditional experimental methods to perturb specific neural circuits in a temporally precise and reversible manner. To address these issues, this proposal will combine a computational model of the spinal sensorimotor system with temporally precise, circuit specific manipulation of the following: a) selective proprioceptive afferent pathways and b) a set of inhibitory spinal interneurons that modulate the strength of proprioceptive feedback in behaving mice. Specifically, two Aims will address key outstanding questions: 1) What are the specific proprioceptive feedback pathways that contribute to stereotyped muscle activation patterns during the acceleration and deceleration phases of limb movement, and during which phases of movement is proprioceptive feedback required (Aim 1)? 2) How does temporally precise modulation of feedback strength (gain) by spinal interneurons ensure appropriate muscle activation patterns (Aim 2)? The overarching hypothesis of this proposal is that the amplitude and timing of agonist and antagonist muscle activity depend critically on temporally precise tuning of selective proprioceptive feedback pathways, and disruption of such feedback causes aberrant and inaccurate movements. Answering these questions will help to uncover the computational logic implemented by sensorimotor pathways for the accurate and efficient execution of rapid movements and reveal how disruption of these pathways produces motor deficits. In addition, by defining spinal circuit mechanisms that control limb movement, this work will lay the groundwork for future studies investigating how descending motor systems recruit spinal circuits to ensure appropriate muscle activation patterns.

项目摘要 准确有效地执行快速，目标指导运动的能力对于与 环境。这些运动为实验和临床研究提供了关键的行为范式， 帮助建立感觉运动控制理论并表征许多神经系统的运动障碍 疾病。特征，倒数的准确执行快速，目标指导的动作可以实现 激活相反的肌肉以时间精确的方式加速和减速肢体。许多 神经系统的感觉运动障碍（例如感觉脱落和小脑病）破坏了 这种特征性的肌肉激活，导致运动性能受损。因此，出现和 这种刻板印象的肌肉招募模式的破坏提供了理论和临床见解 感觉运动电路可实现速度和准确性。然而，建立和控制这一点的神经机制 相互的肌肉募集仍然难以捉摸，在很大程度上是因为本体感受的相对贡献 肌肉的反馈尚未清楚地确​​定。尽管行为观察和 计算模型暗示了本体感受反馈在协调肢体运动中 这些感觉途径在完整的临时精确肌肉激活中的因果作用，行为动物 很难调查。挑战部分是由于传统实验方法无法 以时间精确和可逆的方式扰动特定的神经回路。为了解决这些问题， 提案将将脊柱感觉运动系统的计算模型与时间精确的电路相结合 以下特定操作：a）选择性的本体感知传入途径和b）一组抑制 脊柱中间神经元调节行为小鼠本体感受反馈的强度。具体来说，两个 目的将解决关键问题：1）具体的本体感受反馈途径是什么 在肢体的加速和减速阶段中有助于刻板的肌肉激活模式 运动，在哪个运动阶段是需要本体感知反馈的（AIM 1）？ 2）如何 脊柱中间神经元对反馈强度（增益）的时间精确调制确保适当的肌肉 激活模式（AIM 2）？该提议的总体假设是 激动剂和拮抗剂的肌肉活性急切地取决于选择性本体感受的时间精确调整 反馈途径和这种反馈的破坏会导致异常和不准确的运动。回答 这些问题将有助于发现感觉运动途径实现的计算逻辑 准确有效地执行快速运动，并揭示这些途径的破坏如何产生 运动不足。另外，通过定义控制肢体运动的脊柱电路机制，这项工作将放置 未来研究的基础研究调查了下降运动系统如何募集脊柱电路以确保 适当的肌肉激活模式。